Genomic Fabric Remodeling in Prostate Cancer
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PROVIDER: PRJNA713768 | ENA |
REPOSITORIES: ENA
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Project description:Prostate cancer is a leading cause of death among men but its genomic characterization and best therapeutic strategy are still under debate. The Genomic Fabric Paradigm (GFP) considers the transcriptome as a multi-dimensional mathematical object subjected to a dynamic set of expres-sion correlations among the genes. Here, GFP is applied to gene expression profiles of three (one primary, and two secondary) cancer nodules and the surrounding normal tissue from a surgically removed prostate tumor. GFP was used to determine the regulation and rewiring of the P53 signaling, apoptosis, prostate cancer and several other pathways involved in survival and pro-liferation of the cancer cells. Genes responsible for the block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy and sustained angiogenesis were found as differently regulated in the three cancer nodules with re-spect to the normal tissue. The analysis indicates that even histo-pathologically equally graded cancer nodules from the same tumor have substantially different transcriptomic organizations, raising legitimate questions about the validity of meta-analyses comparing large populations of healthy and cancer humans. The study suggests that GFP may provide a personalized alternative to the biomarkers’ approach of cancer genomics.
2021-03-12 | GSE168718 | GEO
Project description:Genome-wide copy number changes were monitored using array comparative genomic hybridization (aCGH) of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression including precursor lesions, clinically localized disease and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Keywords: Disease state analysis using array-based comparatavie genomic hybridization
2007-07-31 | GSE8026 | GEO
Project description:Paxillin regulates genomic networks in prostate cancer
| PRJNA544533 | ENA
Project description:Patients with aggressive prostate cancer generally present with poor outcomes. Identifying the factors regulating prostate cancer aggressiveness may open new avenues in therapy. Specifically, information from prostate cancer patient databases revealed that higher phosphoenolpyruvate carboxykinase isoform 2 (PCK2) levels correlate with more aggressive tumors and lower survival rates. Herein, we show that high tumorigenic prostate cancer cell clones express high levels of PCK2. We found that elevated levels of PCK2 are critical for the glucose metabolic remodeling and the maintenance of tumor-initiating cells (TICs) in aggressive prostate cancer. Our data suggest that PCK2 promotes tumorigenicity by lowering acetyl-CoA levels through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate cancer. 2 subclones have been isolated from DU145 cells. The epithelial like (EL) clone has a high tumorigenicity ability and enriched tumor initiating cells than mesenchymal like (ML) clone. Genes with differential expression pattern between these two clones were detected by gene micorarray.
2016-01-04 | E-GEOD-76470 | biostudies-arrayexpress
Project description:Obese men are at higher risk of developing advanced prostate cancer and have higher rates of cancer-specific mortality. However, the biological mechanisms explaining these associations are unknown. Using gene expression data, we aimed to identify molecular alterations in prostate cancer tissue associated with obesity. Gene Set Enrichment Analysis identified fifteen gene sets up-regulated in the tumor tissue of obese prostate cancer patients (N=84) compared to healthy weight patients (N=192), five of which were related to chromatin remodeling. These gene sets were not identified in an analysis of adjacent normal tissue. Patients with tumors with high expression of chromatin remodeling genes had worse clinical characteristics (Gleason grade >7, 41% versus 17%, p-trend = 3.21 x 10-4) and poorer prostate cancer-specific survival independent of Gleason grade (lethal outcome, OR = 5.01, 95% CI = 2.31 to 11.38). Mediation analysis further supported a role for chromatin remodeling in the obesity-lethal prostate cancer relationship.
2017-03-01 | GSE79021 | GEO
Project description:The reason why prostate cancer is significantly more common in Western than Asian men is unknown. Using a genome-wide approach to compare the genomic changes in prostate cancer tissues, we determined that those from Chinese patients lack key somatic genomic changes commonly found in Western patients, including the 21q22.2-22.3 deletion which causes the TMPRSS2:ERG fusion gene, and 10q deletion which leads to PTEN inactivation. The results were confirmed and their consequence on ERG expression was identified by study of a large series of Chinese and UK samples using tissue-microarrays. Subsequently, we identified significant AR genotype differences between UK and Chinese prostate cancer patients. The identification of specific somatic genomic differences in cancers from distinct populations may provide an opportunity to identify cancer-causing or protective factors.
2010-05-15 | GSE18333 | GEO
Project description:We profiled the whole transcriptomes of male and female rat hypothalamic paraventricular nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in autism. The rats were prenatally exposed (G15) to betamethasone followed by repeated adiministration of N-Methyl-D-Aspartic acid on postnatal days 12, 13 and 15 which triggered the infantile spasms and autism spectrum disease behavior. Pups were treated with saline on days 13, 14 and 15 prior to NMDA administration. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in autistic rats . The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking. Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics.
2019-03-12 | GSE128091 | GEO
Project description:Background: Metastases result in 90% of all cancer deaths. Prostate cancer primary tumors evolve to become metastatic through selective alterations, such as amplification and deletion of genomic DNA. Methods: Genomic DNA copy number alterations were used to develop a gene signature that measured the metastatic potential of a prostate cancer primary tumor. We studied the genomic landscape of these alterations in 294 primary tumors and 49 metastases from 5 independent cohorts. Receiver-operating characteristic cross-validation and Kaplan-Meier survival analysis were performed to assess the accuracy of our predictive model. The signature was measured in a panel of 337 cancer cell lines from 29 different tissue origins. Results: We identified 399 copy number alterations around genes that were over-represented in metastases and predictive of whether a primary tumor will metastasize. Cross-validation analysis resulted in a predictive accuracy of 80.5% and log rank analysis of the metastatic potential score was significantly related to the endpoint of metastasis-free survival (p=0.014). The metastatic signature was observed in cell lines originating from lung, breast, colon, thyroid, rectum, pancreas and melanoma. The signature was comprised in part of genes of known or putative metastatic role — 8 solute carrier genes, 6 Cadherin family genes and 5 potassium channel genes — that function in metabolism, cell-to-cell adhesion and escape from anoikis/apoptosis. Conclusions: Somatic Copy number alterations are an independent predictor of metastatic potential. The data indicate a prognostic utility for using primary tumor genomics to assist in clinical decision making and developing therapeutics for prostate and likely other cancers.
2013-12-01 | GSE27105 | GEO
Project description:Patients with aggressive prostate cancer generally present with poor outcomes. Identifying the factors regulating prostate cancer aggressiveness may open new avenues in therapy. Specifically, information from prostate cancer patient databases revealed that higher phosphoenolpyruvate carboxykinase isoform 2 (PCK2) levels correlate with more aggressive tumors and lower survival rates. Herein, we show that high tumorigenic prostate cancer cell clones express high levels of PCK2. We found that elevated levels of PCK2 are critical for the glucose metabolic remodeling and the maintenance of tumor-initiating cells (TICs) in aggressive prostate cancer. Our data suggest that PCK2 promotes tumorigenicity by lowering acetyl-CoA levels through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate cancer.
2016-01-04 | GSE76470 | GEO
Project description:Genomic Characterization of Metastatic Castration Resistant Prostate Cancer
| PRJNA479544 | ENA